The brain and its vasculature represents the continuation of a 29 year quest for an understanding of the vasculature of the human brain and its relationship to the function of the human brain in health and disease. Because of the intimate relationship between brain function and the brain vasculature that has been uncovered by ourselves and others, studies of the vascular and metabolic responses to functionally-induced changes in neuronal activity provide a unique window to study the functional organization of the living human brain in health and disease. The pursuit of this goal was greatly enhanced by the development of modern functional imaging techniques beginning in the 1970's with positron emission tomography (PET). The recent addition of functional magnetic resonance imaging (MRI) expands our potential but, at the same time, challenges us to understand more fully the relationship between brain function and brain circulation and metabolism. In this renewal application we propose to combine in one coordinated effort PET, fMRI and magnetic resonance spectroscopy (MRS). These powerful medical imaging techniques will be utilized to determine more precisely the relationship of brain circulation and metabolism to function (especially language) in the normal human brain and in patients with selected disease. In addition, we will determine the most effective role for each of these techniques in this work. PET, fMRI and MRS each have important and, sometimes, unique strengths and weaknesses which needed to be evaluated considered together in determining how they should be employed most effectively. Our ultimate objective is to improve our understanding of human cognition and its disturbance by disease.